DOCSLIB.ORG

International Consensus Guideline for Reporting Transmission Electron Microscopy Results in the Diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
International Consensus Guideline for Reporting Transmission Electron Microscopy Results in the Diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria) Early View Original article International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria) Amelia Shoemark, Mieke Boon, Christoph Brochhausen, Zuzanna Bukowy-Bieryllo, Maria Margherita De Santi, Patricia Goggin, Paul Griffin, Richard G. Hegele, Robert A. Hirst, Margaret W. Leigh, Alison Lupton, Karen MacKenney, Heymut Omran, Jean-Claude Pache, Andreia Pinto, Finn P. Reinholt, Josep Schroeder, Panayotis Yiallouros, Estelle Escudier Please cite this article as: Shoemark A, Boon M, Brochhausen C, et al. International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria). Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.00725-2019). This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Copyright ©ERS 2020 International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria) Amelia Shoemark1,2, Mieke Boon3, Christoph Brochhausen4, Zuzanna Bukowy-Bieryllo5, Maria Margherita De Santi6, Patricia Goggin7, Paul Griffin1,8, Richard G Hegele9, Robert A. Hirst10, Margaret W Leigh11, Alison Lupton12, Karen MacKenney13, Heymut Omran14, Jean-Claude Pache15, Andreia Pinto16, Finn P Reinholt17, Josep Schroeder4, Panayotis Yiallouros18, Estelle Escudier19 *These authors represent a larger guideline development group acknowledged below. 1. Royal Brompton Hospital, London, UK 2. School of Medicine, University of Dundee, UK 3. Department of Pediatrics, University Hospital Leuven, Belgium 4. Institute of Pathology, University Regensburg, Regensberg, Germany 5. Institute of Human Genetics, Polish Academy of Sciences, Poland 6. Department of Pathology, University Hospital of Siena, Italy. 7. University Hospital Southampton NHS Foundation Trust, Southampton, UK 8. Royal Childrens Hospital, Melbourne, Australia 9. Hospital for Sick Children-University of Toronto, Toronto, Ontario, Canada 10. Department of Respiratory Sciences, University of Leicester, Leicester UK 11. Department of Pediatrics and Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina, USA 12. Greater Glasgow and Clyde, Queen Elizabeth University Hospital, Pathology Department, UK 13. NSW Health Pathology, Concord Repatriation General Hospital, Sydney, Australia 14. Department of Pediatrics; University Hospital Muenster; Germany 15. University Hospital of Geneva, Switzerland 16. Instituto de Medicina Molecular, Portugal 17. Oslo University Hospital, Oslo, Norway 18. Medical School, University of Cyprus, Cyprus 19. Sorbonne Université, Faculté de Médecine, INSERM UMR_S933, (APHP) Assistance Publique Hôpitaux de Paris and CHIC (centre hospitalier intercommunal de Créteil), France ABSTRACT Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally. INTRODUCTION Primary Ciliary Dyskinesia (PCD) is a heterogeneous inherited condition affecting 1:10,000 population (1). Symptoms usually begin early in life and include: chronic nasal discharge and wet cough, progressing in childhood to recurrent upper and lower airway infections and eventual bronchiectasis (1). As cilia are also present at the embryonic node defects in nodal cilia may cause abnormalities of left-right laterality determination (situs abnormalities). Diagnosis of PCD usually relies on a combination of tests, because a single test cannot reliably diagnose all PCD types. These tests may include nasal nitric oxide measurement(2), assessment of ciliary waveform by high speed video microscopy(3), immunofluorescence analysis of ciliary proteins(4), transmission electron microscopy (TEM) and genetic testing ).European and North American diagnostic guidelines differ in recommendations for diagnostic testing although both agree that assessment of ciliary ultrastructure by TEM and/ or bi-allelic mutations in a known PCD gene definitively confirm a PCD diagnosis (5-7). However, there has been considerable heterogeneity among pathology reports describing PCD and interpreting what constitutes a diagnostic defect. Defects of the ciliary axoneme can occur secondary to infection or inflammation of the airway mucosa or in samples which have not been adequately prepared. Differences in reporting and interpretation of findings can lead to misdiagnosis. In recent years advances in genetic testing and molecular biology have redefined many aspects of PCD, whilst improving understanding of the basic science has further complicated the use of traditional electron microscopy terminology. For example the use of the term ‘radial spoke defect’ has been used to describe both central complex defects such as those caused by RSPH4A mutations and microtubular disarrangement defects caused by CCDC39 mutations (8-11). In other clinical entities such as renal allograft pathology internationally agreed pathology classification known as ‘the Banff criteria’ has been shown to significantly improve diagnostic precision, reproducibility and disease outcome (12, 13). The aim of the present project was to provide an internationally agreed ultrastructural classification for the diagnosis of PCD by defining defects diagnostic for PCD, describing features which should be included in a report to assist multidisciplinary diagnosis of PCD and define adequacy of a diagnostic sample. METHODS Guideline development The guideline development process is shown in Figure 1. A group of electron microscopy experts (representing 18 centres in 14 countries: Australia, Belgium, Canada, Cyprus, France, Germany, Italy, Norway, Poland, Portugal, Spain, Switzerland, United Kingdom, USA) met in person and via video link to develop a consensus statement for reporting ciliary ultrastructure by TEM at a COST Action BEATPCD meeting. Minutes from this meeting were used to create common themes and identify items for a Delphi consensus survey. The Delphi consensus survey consisted of three rounds with aims to: a) Define defects diagnostic for PCD b) Describe features which should be included in a report to assist multidisciplinary diagnosis of PCD c) Define adequacy of a diagnostic sample Agreement was considered to be met if > 80% of the participants agreed. Consultation with the wider BEATPCD community was conducted at the next BEATPCD meeting. Guideline validation Once a draft guideline was complete a series of TEM sections were distributed among the group and the guideline was tested and modified for inconsistencies and clarity. A list of 16 cases representing patients that had a genetically confirmed diagnosis of PCD or conclusively did not have PCD were used for the guideline validation. Four centres were assigned four cases from the following to prepare: CCDC114, CCDC39, CCDC40, CCNO, DNAAF1, DNAAF3, DNAH5, DNAH11, DRC1, RSPH4A, cystic fibrosis, healthy volunteer (x2), inadequate sample (x2), unaffected sibling of a patient with PCD. Centres at Southampton (UK), Toronto (Canada), Paris (France) and Muenster (Germany) sectioned and stained 4 grids from 4 cases each. These grids were sent to London where they were quality checked, anonymised, randomised and distributed by an individual who was not part of the consensus group. 17 centres then received 4 grids and 1 centre images. Centres did not receive their own grids. All 17 centres assessed the 4 grids, each centre using its own technology for making and interpreting images. The 18th centre received images. The centres completed a report form based on the consensus statement and returned representative images. The form included class of defect, ultrastructural defect, adequacy of the sample and a summary of key findings. One centre reviewed images taken at the distribution centre in London, rather than grids, due to technical difficulties. Results of the validation exercise were discussed in a face to face meeting of the group. One additional online survey
Load more

Recommended publications
  • History Department Botany
    THE HISTORY OF THE DEPARTMENT OF BOTANY 1889-1989 UNIVERSITY OF MINNESOTA SHERI L. BARTLETT I - ._-------------------- THE HISTORY OF THE DEPARTMENT OF BOTANY 1889-1989 UNIVERSITY OF MINNESOTA SHERI L. BARTLETT TABLE OF CONTENTS Preface 1-11 Chapter One: 1889-1916 1-18 Chapter Two: 1917-1935 19-38 Chapter Three: 1936-1954 39-58 Chapter Four: 1955-1973 59-75 Epilogue 76-82 Appendix 83-92 Bibliography 93-94 -------------------------------------- Preface (formerly the College of Science, Literature and the Arts), the College of Agriculture, or The history that follows is the result some other area. Eventually these questions of months ofresearch into the lives and work were resolved in 1965 when the Department of the Botany Department's faculty members joined the newly established College of and administrators. The one-hundred year Biological Sciences (CBS). In 1988, The overview focuses on the Department as a Department of Botany was renamed the whole, and the decisions that Department Department of Plant Biology, and Irwin leaders made to move the field of botany at Rubenstein from the Department of Genetics the University of Minnesota forward in a and Cell Biology became Plant Biology's dynamic and purposeful manner. However, new head. The Department now has this is not an effort to prove that the administrative ties to both the College of Department's history was linear, moving Biological Sciences and the College of forward in a pre-determined, organized Agriculture. fashion at every moment. Rather I have I have tried to recognize the attempted to demonstrate the complexities of accomplishments and individuality of the the personalities and situations that shaped Botany Department's faculty while striving to the growth ofthe Department and made it the describe the Department as one entity.
    [Show full text]
  • Ciliopathiesneuromuscularciliopathies Disorders Disorders Ciliopathiesciliopathies
    NeuromuscularCiliopathiesNeuromuscularCiliopathies Disorders Disorders CiliopathiesCiliopathies AboutAbout EGL EGL Genet Geneticsics EGLEGL Genetics Genetics specializes specializes in ingenetic genetic diagnostic diagnostic testing, testing, with with ne nearlyarly 50 50 years years of of clinical clinical experience experience and and board-certified board-certified labor laboratoryatory directorsdirectors and and genetic genetic counselors counselors reporting reporting out out cases. cases. EGL EGL Genet Geneticsics offers offers a combineda combined 1000 1000 molecular molecular genetics, genetics, biochemical biochemical genetics,genetics, and and cytogenetics cytogenetics tests tests under under one one roof roof and and custom custom test testinging for for all all medically medically relevant relevant genes, genes, for for domestic domestic andand international international clients. clients. EquallyEqually important important to to improving improving patient patient care care through through quality quality genetic genetic testing testing is is the the contribution contribution EGL EGL Genetics Genetics makes makes back back to to thethe scientific scientific and and medical medical communities. communities. EGL EGL Genetics Genetics is is one one of of only only a afew few clinical clinical diagnostic diagnostic laboratories laboratories to to openly openly share share data data withwith the the NCBI NCBI freely freely available available public public database database ClinVar ClinVar (>35,000 (>35,000 variants variants on on >1700 >1700 genes) genes) and and is isalso also the the only only laboratory laboratory with with a a frefree oen olinnlein dea dtabtaabsaes (eE m(EVmCVlaCslas)s,s f)e, afetuatruinrgin ag vaa vraiarniatn ctl acslasisfiscifiactiaotino sne saercahrc ahn adn rde rpeoprot rrte rqeuqeuset sint tinetrefarcfaec, ew, hwichhic fha cfailcitialiteatse rsa praidp id interactiveinteractive curation curation and and reporting reporting of of variants.
    [Show full text]
  • Accuracy of Immunofluorescence in the Diagnosis of Primary Ciliary Dyskinesia
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Accuracy of immunofluorescence in the diagnosis of Primary Ciliary Dyskinesia Amelia Shoemark1,2, Emily Frost 1, Mellisa Dixon 1, Sarah Ollosson 1, Kate Kilpin1, Andrew V Rogers 1 , Hannah M Mitchison3, Andrew Bush1,2, Claire Hogg1 1 Department of Paediatrics, Royal Brompton & Harefield NHS Trust, London, UK 2 National Heart and Lung Institute, Imperial College London, UK 3 Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, UK Correspondence to: Amelia Shoemark Primary Ciliary Dyskinesia Service Electron microscopy unit Department of Paediatrics Royal Brompton Hospital London SW3 6NP Statement of contribution: AS, CH and AB designed the study. EF, KK, SO and AS consented patients, conducted light microscopy, collected nasal brushings and prepared slides. EF and AS conducted IF staining and analysis. MD conducted light and electron microscopy. HM provided genotyping. AS and EF analysed the data. AS, CH and AB drafted the manuscript. All authors contributed to manuscript drafts and preparation. AS is custodian of the data and takes responsibility for its accuracy. Sources of support: This project is funded by a NIHR fellowship awarded to AS and mentored by CH, HM and AB. AB was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London Running head: Immunofluorescence in PCD diagnosis Descriptor number:14.6 Rare paediatric lung disease Word count (excluding abstract and references): 2872 At a Glance Commentary: Scientific Knowledge on the Subject Primary Ciliary Dyskinesia is a genetically heterogeneous chronic condition.
    [Show full text]
  • Ciliopathies Gene Panel
    Ciliopathies Gene Panel Contact details Introduction Regional Genetics Service The ciliopathies are a heterogeneous group of conditions with considerable phenotypic overlap. Levels 4-6, Barclay House These inherited diseases are caused by defects in cilia; hair-like projections present on most 37 Queen Square cells, with roles in key human developmental processes via their motility and signalling functions. Ciliopathies are often lethal and multiple organ systems are affected. Ciliopathies are London, WC1N 3BH united in being genetically heterogeneous conditions and the different subtypes can share T +44 (0) 20 7762 6888 many clinical features, predominantly cystic kidney disease, but also retinal, respiratory, F +44 (0) 20 7813 8578 skeletal, hepatic and neurological defects in addition to metabolic defects, laterality defects and polydactyly. Their clinical variability can make ciliopathies hard to recognise, reflecting the ubiquity of cilia. Gene panels currently offer the best solution to tackling analysis of genetically Samples required heterogeneous conditions such as the ciliopathies. Ciliopathies affect approximately 1:2,000 5ml venous blood in plastic EDTA births. bottles (>1ml from neonates) Ciliopathies are generally inherited in an autosomal recessive manner, with some autosomal Prenatal testing must be arranged dominant and X-linked exceptions. in advance, through a Clinical Genetics department if possible. Referrals Amniotic fluid or CV samples Patients presenting with a ciliopathy; due to the phenotypic variability this could be a diverse set should be sent to Cytogenetics for of features. For guidance contact the laboratory or Dr Hannah Mitchison dissecting and culturing, with ([email protected]) / Prof Phil Beales ([email protected]) instructions to forward the sample to the Regional Molecular Genetics Referrals will be accepted from clinical geneticists and consultants in nephrology, metabolic, laboratory for analysis respiratory and retinal diseases.
    [Show full text]
  • NME8 Rs2718058 Polymorphism with Alzheimer's Disease Risk
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 24 Research Paper NME8 rs2718058 polymorphism with Alzheimer’s disease risk: a replication and meta-analysis Shu-Lei Liu1, Xue-Chun Wang2, Meng-Shan Tan1, Hui-Fu Wang1, Wei Zhang1, Zi-Xuan Wang1, Jin-Tai Yu1, Lan Tan1 1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, PR China 2Department of Radiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, PR China Correspondence to: Lan Tan, email: [email protected] Jin-Tai Yu, email: [email protected] Keywords: NME8, Alzheimer’s disease, association study, polymorphism, meta-analysis Received: March 01, 2016 Accepted: April 11, 2016 Published: April 28, 2016 ABSTRACT Recently, a large meta-analysis of five genome wide association studies (GWAS) has identified that a novel single nucleotide polymorphism (SNP) rs2718058, adjacent to gene NME8 on chromosome 7p14.1, was associated with late-onset Alzheimer’s disease (LOAD) in Caucasians. However, the effect of rs2718058 on other populations remains unclear. In order to explore the relationship between rs2718058 and LOAD risk in a North Han Chinese population, we recruited 984 LOAD cases and 1354 healthy controls that matched for sex and age in this study. The results showed no significant differences in the genotypic or allelic distributions of rs2718058 polymorphism between LOAD cases and healthy controls, even though after stratification forAPOE ε4 status and statistical adjustment for age, gender and APOE ε4 status (p > 0.05). However, a meta-analysis conducted in a sample of 82513 individuals confirmed a significant association between SNP rs2718058 and LOAD risk (OR = 1.08, 95%CI = 1.05–1.11) in the whole population.
    [Show full text]
  • Understanding Cellular Signaling and Systems Biology with Precision: a Perspective from Ultrastructure and Organelle Studies In
    Available online at www.sciencedirect.com Current Opinion in ScienceDirect Systems Biology Understanding cellular signaling and systems biology with precision: A perspective from ultrastructure and organelle studies in the Drosophila midgut Chiwei Xu1, Maria Ericsson2 and Norbert Perrimon1,3 Abstract [1,2]. Interactions between these cell types are critical One of the aims of systems biology is to model and discover to maintaining tissue integrity and gut function. For properties of cells, tissues and organisms functioning as a example, ISCs proliferation and differentiation are system. In recent years, studies in the adult Drosophila gut have controlled by a complex network integrating autocrine provided a wealth of information on the cell types and their and paracrine signals [3,4]; hormones derived from EEs functions, and the signaling pathways involved in the complex regulate EC physiology; and EC-derived factors signal to interactions between proliferating and differentiated cells in the ISCs following gut damage. context of homeostasis and pathology. Here, we document and discuss how high-resolution ultrastructure studies of organelle Despite the body of knowledge about signaling in the gut, morphology have much to contribute to our understanding of how we are still far from understanding how different signals the gut functions as an integrated system. are processed and integrated inside the cell to orchestrate a particular cellular function. As much of the cell is Addresses organized in membrane-bound or membrane-free organ- 1
    [Show full text]
  • Ultrastructure of Secretory and Senescence Phase in Colleters of Bathysa Gymnocarpa and B
    Revista Brasil. Bot., V.33, n.3, p.425-436, jul.-set. 2010 Ultrastructure of secretory and senescence phase in colleters of Bathysa gymnocarpa and B. stipulata (Rubiaceae)1 EMILIO DE CASTRO MIGUEL2, DENISE ESPELLET KLEIN2,3, MARCO ANTONIO DE OLIVEIRA4 and MAURA DA CUNHA2,5 (received: December 11, 2008; accepted: June 10, 2010) ABSTRACT – (Ultrastructure of secretory and senescence phase in colleters of Bathysa gymnocarpa and B. stipulata (Rubiaceae)). Colleters are secretory structures formed by a parenchymatic axis with vascular bundles, bound by a layer of secretory palisade-like epidermis. Some studies regarding the structure of colleters have focused on secretory cells structure, but not distinguished the secretory and senescent phases. Generally, in mucilage-secreting cells such as colleters, the endoplasmic reticulum and Golgi apparatus are involved in secretion production and transport. In these study, colleters structure of Bathysa gymnocarpa K. Schum. and B. stipulata (Vell.) C. Presl. (Rubiaceae) were determined in two phases: a secretory phase and a senescence one. Samples were collected and processed by usual light and electron microscopy techniques. Studied colleters are constituted by an epidermal palisade layer and a central axis formed by parenchymatic cells with rare vascular traces. During the secretory phase, epidermal cells presented a dense cytoplasm, small vacuoles, enhanced rough and smooth endoplasmic reticulum, and a Golgi apparatus close to large vesicles. During the senescence phase epidermal cells presented a disorganized membrane system. No intact organelles or vesicles were observed. The outer cell wall exhibited similar layers to that observed during the secretory phase. The senescent phase is easily defined by the morphology of the colleters, but not well defined at subcellular level.
    [Show full text]
  • Transmission Distortion and Genetic Incompatibilities Between Alleles in A
    bioRxiv preprint doi: https://doi.org/10.1101/2021.06.09.447720; this version posted June 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Transmission distortion and genetic incompatibilities between alleles in a 2 multigenerational mouse advanced intercross line 3 Danny Arends, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 4 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 5 Germany 6 Stefan Kärst, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 7 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 8 Germany 9 Sebastian Heise, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 10 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 11 Germany 12 Paula Korkuc, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 13 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 14 Germany 15 Deike Hesse, [email protected], Albrecht Daniel Thaer-Institut für Agrar- und 16 Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 17 Germany 18 Gudrun A. Brockmann†, [email protected], Albrecht Daniel Thaer-Institut für Agrar- 19 und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Invalidenstraße 42, D-10115 Berlin, 20 Germany 21 † To whom correspondence should be addressed. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.09.447720; this version posted June 10, 2021.
    [Show full text]
  • The Ultrastructure of Pathogenic Bacteria Under Different Ecological Conditions
    The Ultrastructure of Pathogenic Bacteria under Different Ecological Conditions The Ultrastructure of Pathogenic Bacteria under Different Ecological Conditions By Larisa Mikhailovna Somova The Ultrastructure of Pathogenic Bacteria under Different Ecological Conditions By Larisa Mikhailovna Somova This book first published 2020 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2020 by Larisa Mikhailovna Somova All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-4562-8 ISBN (13): 978-1-5275-4562-5 This book is dedicated to George Pavlovich Somov (1917–2009) The outstanding Russian epidemiologist and microbiologist, and founder of the Scientific School of Research Institute of Epidemiology and Microbiology in Vladivostok (Russia) “A life is good only when it is a continuous movement forward from the adolescence to the grave” TABLE OF CONTENTS Foreword .................................................................................................... ix Preface ....................................................................................................... xii Acknowledgements ..................................................................................
    [Show full text]
  • The Ultrastructure of a Typical Bacterial Cell the Bacterial Cell
    A.Kavitha Assistant professor Department of Botany RBVRR Womens college The Ultrastructure Of A Typical Bacterial Cell The Bacterial Cell This is a diagram of a typical bacterial cell, displaying all of it’s organelle. The Bacterial Cell This is what a bacterial cell looks like under an electron microscope. Bacteria come in a wide variety of shapes Perhaps the most elemental structural property of bacteria is their morphology (shape). Typical examples include: coccus (spherical) bacillus (rod-like) spiral(DNA-like) filamentous (elongated) Cell shape is generally characteristic of a given bacterial species, but can vary depending on growth conditions. Some bacteria have complex life cycles involving the production of stalks and appendages (e.g. Caulobacter) and some produce elaborate structures bearing reproductive spores (e.g. Myxococcus, Streptomyces). Bacteria generally form distinctive cell morphologies when examined by light microscopy and distinct colony morphologies when grown on Petri plates. Perhaps the most obvious structural characteristic of bacteria is (with some exceptions) their small size. For example, Escherichia coli cells, an "average" sized bacterium, are about 2 µm (micrometres) long and 0.5 µm in diameter, with a cell volume of 0.6–0.7 μm3.[1] This corresponds to a wet mass of about 1 picogram (pg), assuming that the cell consists mostly of water. The dry mass of a single cell can be estimated as 23% of the wet mass, amounting to 0.2 pg. About half of the dry mass of a bacterial cell consists of carbon, and also about half of it can be attributed to proteins. Therefore, a typical fully grown 1-liter culture of Escherichia coli (at an optical density of 1.0, corresponding to c.
    [Show full text]
  • Ciliary Dyneins and Dynein Related Ciliopathies
    cells Review Ciliary Dyneins and Dynein Related Ciliopathies Dinu Antony 1,2,3, Han G. Brunner 2,3 and Miriam Schmidts 1,2,3,* 1 Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg University Faculty of Medicine, Mathildenstrasse 1, 79106 Freiburg, Germany; [email protected] 2 Genome Research Division, Human Genetics Department, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 KL Nijmegen, The Netherlands; [email protected] 3 Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein Zuid 10, 6525 KL Nijmegen, The Netherlands * Correspondence: [email protected]; Tel.: +49-761-44391; Fax: +49-761-44710 Abstract: Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel Citation: Antony, D.; Brunner, H.G.; developments in the field.
    [Show full text]
  • Novel Gene Discovery in Primary Ciliary Dyskinesia
    Novel Gene Discovery in Primary Ciliary Dyskinesia Mahmoud Raafat Fassad Genetics and Genomic Medicine Programme Great Ormond Street Institute of Child Health University College London A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy University College London 1 Declaration I, Mahmoud Raafat Fassad, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract Primary Ciliary Dyskinesia (PCD) is one of the ‘ciliopathies’, genetic disorders affecting either cilia structure or function. PCD is a rare recessive disease caused by defective motile cilia. Affected individuals manifest with neonatal respiratory distress, chronic wet cough, upper respiratory tract problems, progressive lung disease resulting in bronchiectasis, laterality problems including heart defects and adult infertility. Early diagnosis and management are essential for better respiratory disease prognosis. PCD is a highly genetically heterogeneous disorder with causal mutations identified in 36 genes that account for the disease in about 70% of PCD cases, suggesting that additional genes remain to be discovered. Targeted next generation sequencing was used for genetic screening of a cohort of patients with confirmed or suggestive PCD diagnosis. The use of multi-gene panel sequencing yielded a high diagnostic output (> 70%) with mutations identified in known PCD genes. Over half of these mutations were novel alleles, expanding the mutation spectrum in PCD genes. The inclusion of patients from various ethnic backgrounds revealed a striking impact of ethnicity on the composition of disease alleles uncovering a significant genetic stratification of PCD in different populations.
    [Show full text]